Project description:The present study is aimed at profiling the miRNA expression pattern in oral squamous cell carcinoma (OSCC) and adjacent oral mucosa to develop a new miRNA signature for oral cancer. Agilent Human miRNA Microarray v2.0 (G4470B, Agilent Technologies) was used to identify miRNAs differentially expressed in OSCC. MicroRNA processing was carried out according to the manufacturer’s instructions. Hybridized microarrays were scanned with a DNA microarray scanner (Agilent G2565BA) and features were extracted using the Agilent Feature Extraction (AFE) image analysis tool (version A.9.5.3) with default protocols and settings. Data pre-processing and differential expression analysis were done in R Studio using the Bioconductor AgiMicroRna package.12 The Total Gene Signal provided by the AFE image analysis software was used for data analysis. Data were normalized between arrays using the quantile method. Microarray profiling identified a set of 105 miRNAs to be differentially expressed in OSCC, out of which a subset of 19 most dysregulated miRNAs were considered to formulate the miRNA signature for oral cancer.
Project description:Analysis of Ultra-deep Pyrosequencing and Cloning Based Sequencing of the Basic Core Promoter/Precore/Core Region of Hepatitis B Virus Using Newly Developed Bioinformatics Tools
Project description:<p>Metabolomic profiling was applied to 1,259 sera collected within five years of a lung cancer diagnosis and 8,470 non-case sera from ever-smoker participants in the Prostate Lung Colorectal and Ovarian (PLCO) Study to identify metabolic signatures for the earlier detection of lung cancer. We develop a panel of five lung cancer-associated metabolites (L5MetP: diacetylspermine, creatine riboside, arginine, hypoxanthine, and acylcarnitine C18:1) to assess 1-year risk of lung cancer. In the testing set, the L5MetP achieves an area under the receiver operating characteristic curve (AUC) of 0.79 (95% CI: 0.76-0.82) for 1-year risk of lung cancer. The L5MetP also complements existing clinical risk models that predict risk incident lung cancer as well as those that predict death from lung cancer. The L5MetP provides a means for identifying ever-smoker individuals who are at elevated risk of having lung cancer to inform on the need for lung cancer screening.</p>
Project description:The ability to predict transcription factors based on sequence information in regulatory elements is a key step in systems-level investigation of transcriptional regulation. Here, we have developed a novel tool, IMAGE, for precise prediction of transcription factors based on transcriptome profiling and genome-wide maps of enhancer activity. High precision is obtained by combining a near-complete database of position weight matrices (PWMs), generated by compiling public databases and systematic prediction of PWMs for uncharacterized transcription factors, with a state-of-the-art method for PWM scoring and a novel machine learning strategy, based on both enhancers and promoters, to predict the contribution of motifs to transcriptional activity. We applied IMAGE to published data obtained during 3T3-L1 adipocyte differentiation and showed that IMAGE predicts causal transcriptional regulators of this process with higher confidence than other methods. Furthermore, we generated genome-wide maps of enhancer activity and transcripts during human mesenchymal stem cell commitment and adipocyte differentiation and used IMAGE to identify positive and negative transcriptional regulators of this process. Collectively, our results demonstrate that IMAGE is a powerful and precise method for prediction of regulators of gene expression.
Project description:Purpose: To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Methods: A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results: RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. Conclusions: Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways
Project description:To compare 2 different image creation/processing techniques during a standard CT scan in order to "see" problems in the liver and learn which method provides better image quality. The techniques use new artificial intelligence software to decrease image noise, which helps the radiologist to evaluate.
Project description:Chronic liver disease and cancer are global health challenges. The role of the circadian clock (CC) as a regulator of physiology and disease is well established in animal models. However, in human liver the identity of circadian genes and their epigenetic regulation is unknown. Here, we unraveled the circadian transcriptome and epigenome of human hepatocytes using a human liver chimeric mouse model. We identified genes coding for transcription factors, chromatin modifiers, and critical enzymes which are expressed rhythmically in human hepatocytes, and which differ from the mouse liver circadian transcriptome. Moreover, we show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer world-wide, perturbs the human hepatocellular clock leading to an activation of pathways mediating steatosis, fibrosis and cancer. The HCV-disrupted rhythmic hepatic pathways remained deregulated in patients cured of HCV suggesting a major role in liver cancer development, and in the identification of therapeutic targets.
Project description:The lung is a branched tubular network with two distinct compartments — the proximal conducting airways and the peripheral gas exchange region — separated by a discrete boundary termed the bronchoalveolar duct junction (BADJ). Here we image the developing mouse lung in three-dimensions and show that two nested developmental waves demarcate the BADJ under the control of a global hormonal signal. A first wave of branching morphogenesis progresses throughout embryonic development, generating branches for both compartments. A second wave of conducting airway differentiation follows the first wave but terminates earlier, specifying the proximal compartment and setting the BADJ. The second wave is terminated by a glucocorticoid signaling: premature activation or loss of glucocorticoid signaling causes a proximal or distal shift, respectively, in BADJ location. The results demonstrate a novel mechanism of boundary formation in complex, three-dimensional organs and provide new insights into glucocorticoid therapies for lung defects in premature birth. RNAs were extracted from E14 lungs cultured in control and dexamethasone media for 24 hours using Trizol reagents and Qiagen RNeasy Micro kit. Two control and two treated samples were analyzed.